Posting #3 - Treatment of Tuberculosis in Patients who are HIV positive: The Basics

Posting #3

Treatment of Tuberculosis in Patients who are HIV positive: The Basics

Treatment of patient co-infected with HIV

• Efficacy of both HIV and TB treatment have been shown to be effective for people with an HIV/TB co-infection.

• Drug interactions between the two therapies, adverse reaction of a patient to any of the medications, patient compliance, and drug resistance are the main concerns in prescribing therapies for a co-infection.

• Currently, it is recommended that both therapies are started at the same time.

Recommended initial TB drugs for HIV seropositive or seronegative patients

• Isoniazid (INH) - 300mg PO Qday, Rifamycin (RIF) - 600mg Qday, Pyrazinamide (PZA) - 1500mg PO Qday, Ethambutol (EMB) - 1200mg PO Qday for 7 days/wk for 8 weeks or 5 days/wk for 8 weeks if on DOT

• then INH and RIF for 7day/wk for 18 weeks or 5 days/wk for 18 weeks if on DOT

• Vitamin B-6 (pyridoxine) supplementation should be taken by any patients taking INH and efavirenz

Recommended initial HIV drugs for co-infected patients

• 2 Nucleotide reverse transcriptase inhibitors (nRTI) and efavirenz (a non-nucleotide reverse transcriptase inhibitor [nnRTI])

• nRTI - tenofovir/emtricitabine 300mg/200mg qDay

• nRTI - abacavir/lamivudine 600mg/300mg qDay

• Efavirenz 600mg PO Qhs (800mg for pt >60kg)

Considerations in regards to ART therapy in co-infected patients on rifampin

• Rifampin is a potent CYP3A4 inducers and may decrease serum concentrations of other medications, especially protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI). PIs are CYP3A4 inducers and more study needs to be done to understand their interaction and effect on serum drug levels particularly in combination with rifampin.

• Nonnucleotide reverse transcriptase inhibitors:

  • Efavirenz based ART is recommended for co-infected patients with the dosage of efavirenz increased to 800mg/day for patients over 60kg.

  • Delavirdin should not be used together as AUC is decreased by about 95%.

  • Nevirapine serum levels are reduced by rifampin, although no safety data exists for increasing the dosage of nevirapine

• Single PI use with rifampin is not recommended. Ritonavir is the only PI that can be used with Rifampin. Ritonavir's area under the concentration curve (AUC), a measure of the bioavailability of a drug based on the serum concentrations over time, is reduced 35% by rifampin. Other PIs AUC's are reduced by greater than 80%.

• Dual PI combinations

  • Saquinavir/ritonavir would need to be increased to 400mg/400mg twice daily if taken with rifampin

  • Lopinavir/ritonavir shouldn't be used unless it is pharmaco-augmented for additional ritonavir twice daily, with increased hepatotoxicity from ritonavir likely.

• nucleoside analogs -

• Integrase inhibitors - No dosing changes are recommended, although raltegravir serum levels are reduced

• CCR5 receptor antagonists - maraviroc dosage should be increased when used with rifampin

Considerations in regards to ART therapy in co-infected patient on rifabutin

• Rifabutin is a substrate for CYP3A4, so its concentration may be effected by other medications that are CY3A4 inducers or inhibitors

• Rifabutin has complex interactions with other antivirals, and the interactions have not been well studied, so rifabutin is not generally recommended in this circumstance

• Protease inhibitors:

  • Rifabutin dosage should be reduced when used in combination with ritonavir and a PI, or with a PI alone,

  • Rifabutin shouldn't be used with squinavir alone.

• Nonnucleotide reverse transcriptase inhibitors:

  • Nevirapine and Rifabutin don't change dosages when used together

  • Increase dosage of rifabutin when used with efavirenz

  • Rifabutin and delavirdine shouldn't be used together